There is no admission that the background art disclosed in this section legally constitutes prior art.
Chronic lymphocytic leukemia (CLL) is a progressive B-cell malignancy that demonstrates significant heterogeneity with respect to biology as well as progression-free and overall survival. Due to the lack of survival advantage with early treatment, therapy for CLL is delayed until symptoms develop. Therapeutic regimens for symptomatic CLL have improved significantly over the past decade with introduction of combination therapies that include nucleoside analogs and monoclonal antibodies (chemoimmunotherapy), and for the first time, prolongation of survival is being observed. Unfortunately, even these new chemoimmunotherapy strategies are not curative, and virtually all CLL patients will eventually relapse and succumb to their disease. The lack of curative and effective therapy for all genetic subsets of CLL has fueled investigation of new therapeutic approaches for this disease.
Cyclin-dependent kinases (CDKs) are important regulators that control the timing and coordination of the cell cycle. CDKs form reversible complexes with their obligate cyclin partners to control transition through key junctures in the cell cycle. Endogenous cyclin dependent kinase inhibitory proteins (CDKIs) are known that bind either the CDK or cyclin component and inhibit the kinase activity. Flavopiridol, (cis-5,7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1-methyl)-piperidin-yl]-1-benzopyran-4-one)hydrochloride is a synthetic flavone that has been shown to be a potent and selective inhibitor of the CDKs, and its antitumor activity is related to its CDK inhibitory activity. However, despite promising pre-clinical studies with the cyclin-dependent kinase inhibitor flavopiridol in relapsed chronic lymphocytic leukemia (CLL) and other diseases, previous clinical trials with this agent have been disappointing.
There is clinical evidence that the presence or absence of one or more cytogenetic abnormalities impact the response to various CLL treatments, which in turn influences patient survival and quality of life. Medical professionals would be better equipped to make treatment decisions regarding CLL if they could understand and predict the likely therapeutic response or resistance of the disease to treatment in a particular patient. Accordingly, there is a need for methods and systems which enable the identification of cytogenetic abnormalities that are predictive of response of CLL cells in a patient to one or more treatments or therapeutic agents. Such methods and systems would permit customization of treatment for CLL based on the particular genetic makeup of each patient.
Accordingly, there still remains room for improvement in the treatment of chronic lymphocytic leukemia, and other lymphoproliferative diseases. Accordingly, there is a need for improvement in treating lymphoproliferative diseases.